2-amino[1,3]thiazolo[5,4-a]acridin-11(6H)-one | 138962-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-amino[1,3]thiazolo[5,4-a]acridin-11(6H)-one
• 英文别名: 2-amino-6H-[1,3]thiazolo[5,4-a]acridin-11-one
• CAS: 138962-14-8
• 化学式: C₁₄H₉N₃OS
• 分子量: 267.311
• InChiKey: IOIDDMLZJLPUDE-UHFFFAOYSA-N

物化性质

• 沸点：
  528.1±53.0 °C(Predicted)
• 密度：
  1.504±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino[1,3]thiazolo[5,4-a]acridin-11(6H)-one 在 copper(ll) bromide 、 亚硝酸异戊酯 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以65%的产率得到2-bromothiazolo[5,4-a]acridin-11(6H)-one
  参考文献：
  名称：

  [EN] COMPOUNDS FOR THE TREATMENT OF AMYLOID-ASSOCIATED DISEASES
  [FR] COMPOSÉS POUR LE TRAITEMENT DE MALADIES ASSOCIÉES À LA SUBSTANCE AMYLOÏDE

  摘要：

  这项发明提供了式(I)或(II)或其立体异构体、对映异构体、消旋体或互变异构体的新化合物，其中取代基如规范中所定义。本发明还涉及用作药物的这些新化合物，更具体地用于预防或治疗与淀粉样蛋白相关的疾病，更具体地说是某些神经系统疾病，如被统称为tau病变的疾病，以及由细胞毒性α-突触核蛋白淀粉生成所特征化的疾病。本发明还涉及利用这些新化合物制备对治疗此类淀粉样蛋白相关疾病有用的药物。本发明还涉及包括这些新化合物的药物组合物以及这些新化合物的制备方法。

  公开号：

  WO2016083490A1
• 作为产物：
  描述：

  2-[(2-Amino-1,3-benzothiazol-6-yl)amino]benzoic acid 在 硫酸 作用下， 以87%的产率得到2-amino[1,3]thiazolo[5,4-a]acridin-11(6H)-one
  参考文献：
  名称：

  Thiazolo [5,4-α] acridines

  摘要：

  The synthesis of thiazolo [5,4-a] acridines and acridin-9(10H)-ones by cyclisation of anthranilic acids is described. NMR (specially H-1 NMR) was used to ascertain their 'bent' structure.

  DOI：

  10.1016/s0040-4039(00)93582-2

文献信息

• DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity
  作者：Carole Di Giorgio、Anna Nikoyan、Laetitia Decome、Céline Botta、Maxime Robin、Jean-Pierre Reboul、Anne-Sophie Sabatier、Alain Matta、Michel De Méo

  DOI：10.1016/j.mrgentox.2007.10.022

  日期：2008.2

  The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue (R) viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP 1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (-S9mix). Study of the quantitative structure-activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their, capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation. (C) 2007 Elsevier B.V. All rights reserved.